Our aim is to elucidate the pathogenesis of hypertension which occurs spontaneously in the highly inbred New Zealand strain of rats with genetic hypertension. There are differences between genetically hypertensive and normotensive rats in sodium and body fluid metabolism, in the dependence of vasoconstrictor responses on extracellular calcium and in the role played by the adrenals in blood pressure responses to norepinephrine and sympathetic stimulation in the pithed rat. We will study: (1) The effects on blood pressure, salt and fluid handling and other properties of the cardiovascular system of treatment with anti- hypertensive drugs and other measures (e.g., adrenalectomy, chronic DOCA treatment and chemical sympathectomy). Treatment of rats in the neonatal period will be used to investigate the development of the hypertension. (2) The enhanced vascular reactivity of saline perfused isolated vascular beds (mesenteric arteries, hindquarters and caudal artery); in particular the role of calcium and its transport across the smooth muscle cell membrane. The reasons for the discrepancies in the reactivity of saline - and blood-perfused preparations (mesenteric arteries and hind limb) will be investigated further. (3) Blood pressure responses to pressor and depressor drugs in the whole and pithed rat preparations. The function of vascular beta-receptors will be studied in young and old rats. The investigations will be fully co-ordinated with other studies on experimental hypertension at our Institute.